Serious disorders of the movement automatism, e.g., Parkinson's disease, occur frequently with increasing age.
The cerebral deficiency of neurotransmitters dopamine in the basal ganglions of the brain of the diseased person, in particular, in the corpus striatum, as a consequence of a nigrostrialis degeneration of unknown etiology necessary for the extra pyramidal motoricity, leads to an imbalance between the dopaminogenic and cholinogenic neurotransmitter systems transmitting dopamine which brings about the coordination of movement.
A substitution of the missing biogenous amine can be achieved by supplying its precursor levodopa, which penetrates the blood-brain barrier; said levodopa being absorbed into the dopaminogenic neurons and decarboxylated into dopamine. (Birkmayer, Hornkiewics, Wien, Klin. Wochenschrift 73 (1961), 787.) It is known that the peripheral dopadecarboxylation of levodopa by the simultaneous oral administration of a suitable decarboxylase inhibitor, e.g., carbidopa (DE-PS 30 12 602, U.S. Pat. No. 3,769,424), or benserazide (DE-PS 32 35 093) is largely suppressed, resulting in a distinct increase of the levodopaserum level, which renders possible a relevant reduction of the therapeutically necessary dosage and a decrease of associated gastrointestinal and cardiovascular side effects.
The manufacture of capsules and film tablets containing levodopa and carbidopa, and tablets capable of floating in the gastric fluid (GB-PS 1 243 474, U.S. Pat. No. 4,424,235, BE-PS 894 376), is known. Furthermore, international standards have required, up to the present, a very fast in vitro liberation (USP XXI). In addition, methods for the manufacture of pharmaceutical preparations, from which the medicinal substances levodopa and carbidopa are released slowly and simultaneously, are known. These pharmaceutical preparations, for example, can be polymer matrices (EP-PS 0 253 490, EP-PS 0 320 051), pellets (DE-PS 38 41 955, EP-PS 0 260 236, EP-PS 0 324 947), or also multi-layered molded shapes (EP-PS 0 302 693, EP-PS 0 314 206).
It is also known that the transformation of a medicinal substance, or of a medicinal substance mixture, into a medicinal formulation is essential for influencing the bioavailability. At the same time, it is known to make manageable very low drug dosages by means of suitable pharmaceutical adjuvants, or, as the case may be, to counteract drug incompatibilities in drug mixtures, or to guarantee the chemical stability of one or several drugs. Furthermore, for the manufacture of tablets, a multitude of procedures are known, the aim of which is to transfer pulverized drugs, or mixtures of pulverized drugs and pharmaceutical adjuvants, into tablets under technical conditions. It is known that, by means of an addition of suitable pharmaceutical adjuvants to the drugs or the drug-adjuvant mixtures, it is possible to influence and change the characteristics of the compositions, e.g., stability, electrostatic charge, flow characteristics and tableting characteristics, as well as their bioavailability.
Also, filling hard gelatin capsules with medicinal substances containing powder mixtures, granules, pellets, and similar materials, has been described.
It is also known that by the addition of polyvinylalcohols, a significant delay of the drug liberation can be obtained (DD-WP A 61 K/309 487.4; U. Meyer, Diss., Berlin 1977), and that, in general, quickly decomposing solid tablets can be manufactured with polyvinyl alcohol (W. Rietschel, "die Tablette," 104, Aulendorf, 1966).